G-CSF in Decompensated Cirrhosis: an Open Label Trial

Cirrhosis, Liver Clinical Trial

Official title:

Granulocyte Colony Stimulating Factor in Decompensated Cirrhosis: an Open Label Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03415698
• Other study ID #: GCSF in cirrhosis
• Status: Recruiting
• Phase: Phase 2/Phase 3
• First received: January 11, 2018
• Last updated: January 23, 2018
• Start date: July 2016
• Est. completion date: December 2018

Study information

• Verified date: January 2018
• Source: Postgraduate Institute of Medical Education and Research
• Contact: Virendra Singh, DM
• Phone: 7087009338
• Email: virendrasingh100[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Globally, cirrhosis is the fifth commonest cause of mortality. Its natural history is typified by an initial, largely asymptomatic, "compensated" phase followed by "decompensation" due to complications of raised portal pressures and hepatocellular dysfunction.

Currently the only definitive treatment option for cirrhosis is liver transplantation which is limited in its applicability due to donor shortage, exorbitant costs and lack of widespread availability. The need for long term immunosuppression and its attendant complications are a further drawback. The ability of stem cells to differentiate into multiple cellular lineages makes one speculate that they can be used for tissue repair and regeneration when tissue-resident stem cells become overwhelmed. Bone marrow derived stem cells have amazing plasticity. They can "home" to the liver in response to injury and help in liver regeneration by trans-differentiation, cell fusion and augmentation of tissue- resident stem cell mediated repair. Two methods are available for the mobilisation of stem cells from the bone marrow to the liver. One involves the administration of cytokines like granulocyte-colony stimulating factor (G-CSF) and the other is the isolation of stem cells from the marrow followed by their injection into the hepatic artery or portal vein after purification. The latter is probably more cumbersome and may be potentially risky due to the underlying coagulation abnormalities in cirrhotic patients .

G-CSF has been shown to mobilise bone marrow stem cells and even increase survival in patients of severe alcoholic steatohepatitis and ACLF. There is conflicting evidence on the role of G-CSF in decompensated cirrhosis with some studies showing improved survival while others have shown a lack of clinical or biochemical benefit. Many of these studies have used a single course of G-CSF. Verma et al, in a recent study published in 2018, elegantly demonstrated the beneficial effect of multiple courses of G-CSF in improving mortality and transplant free survival in decompensated cirrhotics.

The investigators too speculate that multiple cycles of G-CSF could result in better outcomes in decompensated cirrhosis by causing more prolonged and sustained stem cell homing to the liver. Thus, this study is being undertaken to further evaluate the safety and efficacy of multiple cycles of G-CSF in decompensated cirrhotics.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2018
• Est. primary completion date: July 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Decompensated Cirrhosis of liver irrespective of etiology

Exclusion Criteria:

• Acute on chronic liver failure (fulfilling either APASL or CANONIC criteria of ACLF)

• Splenic diameter of more than 18 cm

• Concomitant HCC or other active malignancy

• Upper gastrointestinal bleeding in the previous 7 days

• Portal vein thrombosis

• Severe renal dysfunction as defined by creatnine > 1.5mg/dl

• Severe cardiac dysfunction

• Uncontrolled diabetes (Hb A 1c = 9) or diabetic retinopathy

• Acute infection or disseminate intravascular coagulation

• Active alcohol abuse in last 3 months

• Known hypersensitivity to G-CSF

• HIV co-infection

• Pregnancy

• Refusal to give informed consent

Related Conditions & MeSH terms

• Cirrhosis, Liver
• Fibrosis
• Liver Cirrhosis

Intervention

Drug:
• G-CSF
G-CSF will be administered at the dosage of 5 µg/Kg subcutaneously every 12 hr for five consecutive days. four such cycles will be administered at three monthly intervals.
• Standard Medical Therapy
Nutritional support, rifaximin, lactulose, bowel wash, albumin, diuretics, multivitamins and antibiotics.

Locations

Country	Name	City	State
India	Post Graduate Institute of Medical Education and Research	Chandigarh

Sponsors (1)

Lead Sponsor	Collaborator
Postgraduate Institute of Medical Education and Research

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival	Survival at 1 year after start of therapy	One year
Secondary	Hemopoieticstem cell mobilisation	Mobilisation of CD 34+ cells in peripheral blood	One Year
Secondary	Clinical improvement in liver functions	Occurrence of decompensations namely ascites, hepatic encephalopathy and variceal bleed	One Year
Secondary	Biochemical improvement in liver functions	Improvment in MELD score	One year
Secondary	Improvement in nutritional status	Nutritional status will be assesses by skeletal muscle index measurement using CT scan measurements at L3 level	One Year
Secondary	Improvement in quality of life	Quality of life will be assessed using SF-36V2 Health Survey questionnaire	One year
Secondary	Safety of G-CSF as assessed by its adverse effects		One Year